Syk-mediated translocation of PI3Kδ to the leading edge controls lamellipodium formation and migration of leukocytes

Jürgen Schymeinsky, Cornelia Then, Anca Sindrilaru, Ronald Gerstl, Zoltán Jakus, Victor L J Tybulewicz, Karin Scharffetter-Kochanek, Barbara Walzog

Research output: Contribution to journalArticle

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Abstract

The non-receptor tyrosine kinase Syk is mainly expressed in the hematopoietic system and plays an essential role in β2 integrin-mediated leukocyte activation. To elucidate the signaling pathway downstream of Syk during β2 integrin (CD11/ CD18)-mediated migration and extravasation of polymorphonuclear neutrophils (PMN), 'we generated neutrophil-like differentiated HL-60 (dHL-60) cells expressing a fluorescently tagged Syk mutant lacking the tyrosine residue at the position 323 (Syk-Tyr323) that is known to be required for the binding of the regulatory subunit p85 of the phosphatidylinositol 3-kinase (PI3K) class IA-Syk-Tyr323 was found to be critical for the enrichment of the catalytic subunit p110d of PI3K class IA as well as for the generation of PI3K products at the leading edge of the majority of polarized cells. In accordance, the translocation of PI3K p110δ to the leading edge was diminished in Syk deficient murine PMN. Moreover, the expression of EGFP-Syk Y323F interfered with proper cell polarization and it impaired efficient migrition of dHL-60 cells. In agreement with a major role of β2 integrins in the recruitment of phagocytic cells to sites of lesion, mice with a Syk-deficient hematopoietic system demonstrated impaired PMN infiltration into the wounded tissue that was associated with-prolonged cutaneous wound healing. These data imply a novel role of Syk via PI3K p110δ signaling for β2. integrin-mediated migration which is a prerequisite for efficient PMN recruitment in vivo.

Original languageEnglish
Article numbere1132
JournalPLoS One
Volume2
Issue number11
DOIs
Publication statusPublished - Nov 7 2007

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Phosphatidylinositol 3-Kinase
pseudopodia
Pseudopodia
phosphatidylinositol 3-kinase
integrins
neutrophils
leukocytes
Leukocytes
Integrins
Hematopoietic System
Neutrophils
Neutrophil Infiltration
HL-60 Cells
tyrosine
cells
phagocytes
mice
protein subunits
Phagocytes
tissue repair

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Schymeinsky, J., Then, C., Sindrilaru, A., Gerstl, R., Jakus, Z., Tybulewicz, V. L. J., ... Walzog, B. (2007). Syk-mediated translocation of PI3Kδ to the leading edge controls lamellipodium formation and migration of leukocytes. PLoS One, 2(11), [e1132]. https://doi.org/10.1371/journal.pone.0001132

Syk-mediated translocation of PI3Kδ to the leading edge controls lamellipodium formation and migration of leukocytes. / Schymeinsky, Jürgen; Then, Cornelia; Sindrilaru, Anca; Gerstl, Ronald; Jakus, Zoltán; Tybulewicz, Victor L J; Scharffetter-Kochanek, Karin; Walzog, Barbara.

In: PLoS One, Vol. 2, No. 11, e1132, 07.11.2007.

Research output: Contribution to journalArticle

Schymeinsky, J, Then, C, Sindrilaru, A, Gerstl, R, Jakus, Z, Tybulewicz, VLJ, Scharffetter-Kochanek, K & Walzog, B 2007, 'Syk-mediated translocation of PI3Kδ to the leading edge controls lamellipodium formation and migration of leukocytes', PLoS One, vol. 2, no. 11, e1132. https://doi.org/10.1371/journal.pone.0001132
Schymeinsky, Jürgen ; Then, Cornelia ; Sindrilaru, Anca ; Gerstl, Ronald ; Jakus, Zoltán ; Tybulewicz, Victor L J ; Scharffetter-Kochanek, Karin ; Walzog, Barbara. / Syk-mediated translocation of PI3Kδ to the leading edge controls lamellipodium formation and migration of leukocytes. In: PLoS One. 2007 ; Vol. 2, No. 11.
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